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Drafted in December 2008 but never finalized, unsurprisingly there were significant similarities between this FDA draft guideline and the EMA guideline, certainly in terms of the key principles such as the TTC, the acceptance of a staged approach where study duration is limited, and the use of SAR evaluation.

There were though areas of concern the most significant perhaps was the suggestion of the need to introduce lower limits for different patient populations, specifically pediatric populations. Additional safety factors of 3 and 10 were mentioned and suggested for consideration. The need for this additional level of control for pediatric medicines was unclear when considered in the context of the extremely conservative assumptions that form the basis of the calculated TTC control.

Additionally, other subtler differences also existed, including differences in staged TTC values in relation to very short (less than 14 days) studies; the FDA favoring the extension of the 120 μg/day for the whole of this period.

Taken together the differences between the two guidelines would ultimately present anyone faced with having to comply with both with a challenge. It was the recognition of these challenges and others described in more detail below that led to establishment of an ICH process to deliver what became ICH M7. The development of ICH M7 is discussed in Chapter 2.